The UNC Viral Vector Core Facility is essential in our effort to develop gene therapy for cystic fibrosis and other pulmonary diseases. The Vector Core has supported the UNC Gene Therapy for Cystic Fibrosis (CF) projects since 1993 and has achieved a great deal of status in the gene therapy community as a reliable and cost-effective source of recombinant virus vector reagents. The core routinely makes available vectors that are unavailable and/or prohibitively expensive if purchased commercially. Rapid growth in demand for these reagents in recent years has brought us to a mature stage of consistent operation. We are fully staffed, wellequipped, and have the benefit of a commitment for excellent working space for the foreseeable future. These achievements have been accomplished by rapid incorporation of new technological developments as they become available, and by a commitment to making the proceeds of these technologies as widely accessible to researchers as possible. The pursuit of these goals will continue within the proposed research program. In Project 1, the Vector Core will be responsible for the large-scale production and purification of genetically shuffled and phenotypically selected chimeric rAAV vectors, thus facilitating the characterization of these reagents. Additionally, the Core will broaden its production techniques for rAAV to increase our ability to produce vectors more efficiently and on a larger scale. This will entail the use of continuous cell lines induced by helper virus infection, using mammalian as well as SF-9 insect cells. In Project 2, new EIAV producer cell lines will be used in the Vector Core to generate lentivirus vectors with greater safety and predictability. For Project 3, the Vector Core will institute production of RSV vectors as they are developed over the course of the PPG cycle. Through these functions, and in conjunction with other Cores in this application, the Vector Core will support research towards the development of safe and effective gene therapy for CF.